A Phase III Randomized Trial of Low-Dose Versus Standard-Dose mBACOD Chemotherapy With rGM-CSF for Treatment of AIDS-Associated Non-Hodgkin's Lymphoma

October 26, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

To determine the impact of dose intensity on tumor response and survival in patients with HIV-associated non-Hodgkin's lymphoma (NHL).

HIV-infected patients are at increased risk for developing intermediate and high-grade NHL. While combination chemotherapy for aggressive B-cell NHL in the absence of immunodeficiency is highly effective, the outcome of therapy for patients with AIDS-associated NHL has been disappointing. Treatment is frequently complicated by the occurrence of multiple opportunistic infections, as well as the presence of poor bone marrow reserve, making the administration of standard doses of chemotherapy difficult. A recent study was completed using a low-dose modification of the standard mBACOD (cyclophosphamide, doxorubicin, vincristine, bleomycin, dexamethasone, methotrexate ) treatment. A 46 percent response rate was observed in patients treated with this combination of chemotherapeutic agents, with a number of durable remissions and reduced toxicity when compared to previous experience with more standard treatments. A subsequent study showed similar effectiveness using a lower dose of methotrexate administered on day 15. It is hoped that the use of sargramostim (granulocyte-macrophage colony-stimulating factor; GM-CSF) will improve bone marrow function and allow for administration of a higher dose of chemotherapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

HIV-infected patients are at increased risk for developing intermediate and high-grade NHL. While combination chemotherapy for aggressive B-cell NHL in the absence of immunodeficiency is highly effective, the outcome of therapy for patients with AIDS-associated NHL has been disappointing. Treatment is frequently complicated by the occurrence of multiple opportunistic infections, as well as the presence of poor bone marrow reserve, making the administration of standard doses of chemotherapy difficult. A recent study was completed using a low-dose modification of the standard mBACOD (cyclophosphamide, doxorubicin, vincristine, bleomycin, dexamethasone, methotrexate ) treatment. A 46 percent response rate was observed in patients treated with this combination of chemotherapeutic agents, with a number of durable remissions and reduced toxicity when compared to previous experience with more standard treatments. A subsequent study showed similar effectiveness using a lower dose of methotrexate administered on day 15. It is hoped that the use of sargramostim (granulocyte-macrophage colony-stimulating factor; GM-CSF) will improve bone marrow function and allow for administration of a higher dose of chemotherapy.

Patients are randomized to one of two treatment groups. Patients are stratified for (1) presence or absence of a prior AIDS diagnosis, (2) Karnofsky performance status of 70 or greater and lower than 70. Treatment includes prophylaxis for meningeal lymphoma and Pneumocystis carinii pneumonia. Patients on low-dose mBACOD who experience neutropenia may be given rGM-CSF until the absolute neutrophil count improves. AZT may be initiated at the completion of chemotherapy for all patients in complete remission at that time.

PER AMENDMENT 5/30/95: This trial was closed to accrual on 11/7/94 on the recommendation of the Data and Safety Monitoring Board (DSMB), because the non-significant difference in survival between the 2 treatment groups was not expected to change with further enrollment.

Study Type

Interventional

Enrollment

250

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA CARE Center CRS
      • Los Angeles, California, United States, 900331079
        • USC CRS
      • San Francisco, California, United States, 941102859
        • Ucsf Aids Crs
    • Colorado
      • Aurora, Colorado, United States, 80262
        • University of Colorado Hospital CRS
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University CRS
      • Chicago, Illinois, United States, 60612
        • Rush Univ. Med. Ctr. ACTG CRS
    • Indiana
      • Indianapolis, Indiana, United States, 462025250
        • Indiana Univ. School of Medicine, Infectious Disease Research Clinic
    • Maryland
      • Baltimore, Maryland, United States
        • Johns Hopkins Adult AIDS CRS
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess - East Campus A0102 CRS
      • Boston, Massachusetts, United States, 02118
        • Beth Israel Deaconess Med. Ctr., ACTG CRS
      • Boston, Massachusetts, United States
        • Bmc Actg Crs
    • Missouri
      • Saint Louis, Missouri, United States
        • Washington U CRS
    • New York
      • Buffalo, New York, United States, 14215
        • SUNY - Buffalo, Erie County Medical Ctr.
      • New York, New York, United States, 10016
        • NY Univ. HIV/AIDS CRS
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Ctr.
      • New York, New York, United States, 02215
        • Beth Israel Med. Ctr. (Mt. Sinai)
      • Rochester, New York, United States, 14642
        • Univ. of Rochester ACTG CRS
    • North Carolina
      • Chapel Hill, North Carolina, United States, 275997215
        • Unc Aids Crs
    • Ohio
      • Cleveland, Ohio, United States
        • Case CRS
      • Columbus, Ohio, United States, 432101228
        • The Ohio State Univ. AIDS CRS
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hosp. of the Univ. of Pennsylvania CRS
      • Pittsburgh, Pennsylvania, United States, 15213
        • Pitt CRS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Concurrent Medication:

Required:

  • PCP prophylaxis with Bactrim, aerosolized pentamidine, or dapsone.

Allowed:

ddI, except when patient is also taking allopurinol.

Patients must have the following:

  • Diagnosis of HIV seropositivity and non-Hodgkin's lymphoma.
  • Ability to give informed consent and willingness to comply with all procedures and visit schedule.
  • If between ages of 12 and 18 must receive care under direct supervision of a pediatric oncologist, and have consent of parent, guardian, or person with power of attorney.
  • Participation in clinical trials of other antiretroviral agents is at the discretion of the investigator and individual patient.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

  • Active opportunistic infection, excluding Mycobacterium avium complex, requiring antibiotic therapy.
  • Another prior or current malignancy, excepting curatively treated cervical or basal cell carcinoma.
  • Kaposi's sarcoma if rapidly progressive, with visceral involvement, or causing peripheral edema.
  • Primary central nervous system lymphoma.

Concurrent Medication:

Excluded:

  • Zidovudine (AZT) or any antiretroviral agent unless allowed by investigator. ddI is allowed except when also taking allopurinol.

Systemic myelosuppressive drugs, including trimethoprim/sulfamethoxazole (T/S), pyrimethamine/sulfa, or ganciclovir.

-

Patients with the following are excluded:

  • Active opportunistic infection, excluding Mycobacterium avium complex, requiring antibiotic therapy.
  • Another prior or current malignancy, excepting curatively treated cervical or basal cell carcinoma.
  • Kaposi's sarcoma if rapidly progressive, with visceral involvement, or causing peripheral edema.
  • Primary central nervous system lymphoma.

Prior Medication:

Excluded:

  • Immunomodulating agents within 2 weeks of study entry.

Prior Treatment:

Excluded:

  • Chemotherapy.

Radiation therapy as outlined in protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Masking: NONE

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Schering-Plough

Investigators

  • Study Chair: L Kaplan
  • Study Chair: AA Levine
  • Study Chair: DJ Straus

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (ACTUAL)

February 1, 1996

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (ESTIMATE)

August 31, 2001

Study Record Updates

Last Update Posted (ACTUAL)

November 3, 2021

Last Update Submitted That Met QC Criteria

October 26, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 142
  • 11117 (REGISTRY: DAIDS ES Registry Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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